Alzheimer's disease (AD) will become a public health crisis within the next 25 years if left unchecked. Despite the lack of proven treatments that delay the onset or prevent disease progression, several promising candidates are being developed. There is therefore an urgent need for antecedent biomarkers that will identify individuals with AD pathology but who are still cognitively normal ("preclinical AD"), a group in which targeted therapies would likely have the greatest clinical impact. Such biomarkers would also aid in assessing response to potential disease-modifying therapies in clinical trials and in practice. Our biomarkers program was developed and operates within the existing Alzheimer's Disease Research Center (ADRC) and two affiliated Program Project Grants ("The Adult Children Study" (ACS) and "Healthy Aging and Senile Dementia" (HASD)). While most of our scientific aims are being supported by these grants, our needs have grown well beyond the scope of the currently budgeted projects. As a supplement to the ACS, we propose to establish a Biomarkers Core that will provide the infrastructure for the standardized collection, storage, tracking and sharing of samples and the many biomarker data obtained from them. The specific aims of the Biomarkers Core are to: 1) establish a repository for fasted CSF and plasma samples for present and future AD biomarker studies; 2) obtain additional measures in CSF and/or plasma that are not currently obtained in the ACS or HASD that may help to define AD risk in middle-aged cohorts; 3) coordinate the distribution of CSF and plasma samples to qualified AD investigators; and 4) test and establish the measurement reliability of defined biomarkers and begin to explore possible biologic and methodologic sources of variability, important issues that have been inadequately addressed in the field to date. Data management and resource sharing functions will be implemented via a secure, web-based, relational database that is currently under final stages of development. A Biomarkers Core will facilitate research across the various projects of the ACS and HASD by greatly improving capacity and efficiency, as well as foster protocol standardization efforts and promote and facilitate collaborative research within the greater AD scientific community. Such collaborations are essential if the field is to move forward in discovering antecedent biomarkers, with the goal of bringing a truly useful biomarker(s) to the bedside. [unreadable] [unreadable] [unreadable]